武汉云克隆科技股份有限公司

Abstract

AIMS:

Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive.

METHODS AND RESULTS:

Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo.

CONCLUSION:

This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

摘要

目的：

含有多种类黄酮的松树皮提取物被用于传统医药中。碧萝芷是法国海岸松的一种专有树皮提取物，具有抗氧化、抗炎、抗血小板的作用。然而，碧萝芷对内皮功能紊乱的影响仍是难以捉摸的，内皮功能紊乱是动脉粥样硬化和心血管相关疾病的先兆。

方法和结果：

23名冠状动脉疾病（CAD）患者完成了这个随机、双盲、安慰剂对照的交叉性研究。患者在标准心血管治疗的基础上，连续8周摄入碧萝芷（200毫克/天），之后服用安慰剂，反之亦然。在这两个疗程之间，安排了一个2周的冲洗期。在每个治疗期的基线和之后，应用高分辨率超声、氧化应激和炎症的生物标志物、血小板粘附和24小时血压监测等方法，通过对肱动脉血流介导性扩张（FMD）的评估来进行内皮功能非侵入性评估。在冠心病患者中，碧萝芷治疗与血流介导性扩张的改善相关，从5.3±2.6到7.0±3.1（P<0.0001），而使用安慰剂则没有差异（5.4±2.4和4.7±2.0；P = 0.051)。研究小组之间的差异是显著的[估计的治疗效果2.75；95%置信区间（CI）：1.75，3.75，P<0.0001]。15-F(2t)-Isoprostane，一种氧化应激的指数，在碧萝芷治疗后从0.71±0.09显著减少至0.66±0.13，而安慰剂组没有观察到变化（平均差异0.06 pg/ml，95%的置信区间（0.01，0.11），P=0.012）。在用碧萝芷或安慰剂治疗后，炎症标志物、血小板粘附性和血压没有变化。

结论：

这项研究首次证明了抗氧化剂碧萝芷可以通过减少氧化应激改善冠心病患者的内皮功能。

使用试剂原文信息：Quantitative detection of soluble Intercellular Adhesion Molecule-1 (sICAM-1), soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble CD40 Ligand (sCD40L) (all Bender Med Systems, Vienna, Austria), oxidized LDL (oxLDL) (Immundiagnostik, Bernsheim, Germany) and of Lipoprotein-associated phospholipase A2 (Lp-PLA2) (Uscn Life Sciences Inc., Wuhan, China) was performed using enzyme-linked immunosorbent assays (ELISA) according to the manufacturer’s instructions.